An efficient regiospecific synthesis of 2,4,6-trisubstituted pyrimidine-5-carboxaldehydes

ORGN 156

Bo-Liang Deng, deng@purdue.edu, Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Cancer Center, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907 and Hicham Fenniri, hicham.fenniri@ualberta.ca, National Institute for Nanotechnology and Department of Chemistry, University of Alberta, ECERF: 9107-116 Street, Edmonton, AB T6G 2V4, Canada.
Pyrimidines represent an interesting pharmacophore widely distributed on natural and on synthetic products that display an ample variety of relevant biological properties. Specifically substituted pyrimidines are valuable intermediates for drug discovery. Especially, pyrimidine-5-carboxaldehyde is a useful building block for more elaborate groups at position five or for fusing rings onto the original pyrimidine. We are particularly interested in exploiting the versatility of the metal-catalyzed cross-coupling reaction to prepare pyrimidopyrimidine, in view of their potentially interesting molecular recognition to form resotte nanotube. We need to have different amino substitution in the 2- and 6-positions of the pyrimidine-5-carboxaldehyde nucleus as this should allow elaboration to pyrimidopyrimidine. However, there will be a potential problem of the formation of imine with the formyl group at the 5-position of the pyrimidine-5-carboxaldehyde, especially with arylamine. We would like to report a simple and straightforward methodology toward the synthesis of novel 2, 4, 6-trisubstituted pyrimidine-5-carboxaldehydes. Several single X-ray crystals have confirmed the structure assignments.